Study Establishes Effective PRRT Dose

A neuroendocrine tumor (NET) is a type of tumor that originates in endocrine or nerve cells. These cells are found in many organs in the body, including the intestines, lungs, and pancreas. Some NETs are cancerous tumors that require treatment. Since they can originate in hormone-producing cells, NETs can cause a variety of symptoms triggered by hormone fluctuations.

Non-functional tumors do not produce hormones; they account for 60 percent of NETs. NETs that do produce hormones are categorized as functional. Their hormonal activity causes strong symptoms, making them easier to diagnose. For example, functional NETs can result in carcinoid syndrome; such cases experience symptoms like glucose blood level fluctuation and anxiety, which are triggered by hormone release.

Classification of NETs is based on size, location, spread, and microscopic appearance. The size of the tumor, its location, and its degree of spread in the body determine its stage.

Early-stage NETs are typically small and limited to a single organ or layer, while later stages indicate more extensive spread to neighboring lymph nodes and other organs. Pathologists examine tumors under the microscope to ascertain the exact type of NET. During microscopic examination of NET specimens, pathologists classify tumors according to degree of differentiation and proliferation rate.

Treatment regimens for NETs depend on tumor type and stage. In addition to traditional therapies such as chemotherapy and surgery, NETs can be treated with peptide receptor radionuclide therapy, or PRRT, which works by targeting somatostatin receptors on the tumor cell surface.

PRRT is suitable for somatostatin receptor-positive (SRP) tumors. If tumor cells do not express somatostatin receptors, the therapy will be ineffective against the tumor. Currently, the standard treatment for late-stage SRP NETs is PRRT with 177Lu-DOTATATE, a radioactive drug that binds to somatostatin receptors and enters tumor cells. Once inside the cells, the drug builds up and emits radiation that damages the tumor.

Chemical formulation and dosing play an important role in the effectiveness of PRRT. When administered alone, 177Lu-DOTATATE is usually eliminated from the patient’s body rapidly. A recent study published in the Journal of Nuclear Medicine aimed to maximize the therapeutic effect of the drug.

By modifying 177Lu-DOTATATE with a special dye called Evans blue, the researchers extended its availability in the body, therefore boosting its effect against tumor cells. The modified drug, now dubbed 177Lu-DOTA-EB-TATE, was the main focus of the study, which evaluated the effectiveness of different doses to identify the ideal dose for safe, effective NET treatment.

A total of 32 patients diagnosed with SRP NETs participated in the study. They were randomly assigned to three groups receiving different drug doses: 1.17, 1.89, and 3.97 GBq per cycle. Over the course of three cycles, all patient groups tolerated the modified drug well, with no significant side effects. The study findings demonstrated that 177Lu-DOTA-EB-TATE doses of 1.89 and 3.97 GBq per cycle were both effective in controlling NET tumors.

Based on the study findings, modified PRRT is a promising treatment modality. It demonstrates increased effectiveness against NETs and can significantly reduce mortality in late-stage NET patients.

Immunotherapy Cancer Study Shows

Cancer research investigates various aspects of this disease, including its diagnosis and treatment. Over the years, cancer treatment has developed into several categories: chemotherapy, radiation therapy, hormone therapy, surgery, stem cell transplant, and immunotherapy.

Immunotherapy relies on the patient’s immune system as a line of defense against cancer cells. As a form of biological therapy, immunotherapy uses substances produced by living organisms to target cancer.

Although the immune system can attack cancer cells, some types of cancer cells can escape one’s immune defenses. Immunotherapy aims to boost the immune system so that it can more effectively fight cancer. Encompassing many subtypes, immunotherapy utilizes the following: monoclonal antibodies, immune system modulators, checkpoint inhibitors, and T-cell transfer therapy.

T-cell transfer therapy is a subtype of immunotherapy that enhances the immune properties of one’s T cells. T cells are a type of white blood cell that is characterized by a T-cell receptor on its surface. They are produced in the bone marrow, then multiply and mature in the thymus. In their maturation stage, T cells differentiate into one of four types: helper, regulatory, memory, or cytotoxic.

Cytotoxic T cells, also known as CD8+ T cells, mainly function as the body’s defense against infections (bacterial and viral) and tumors. T-cell transfer therapy utilizes cytotoxic T cells to boost the patient’s immunity in the face of cancer.

The T-cell transfer therapy method typically entails extracting a sample of the patient’s T cells and multiplying them in the lab to generate a huge amount to be reinjected into the patient’s body. This therapy can also modify the T cells prior to injection. For example, T cells can be engineered in the lab and transformed into CAR T cells that are equipped with an extra protein that increases their ability to bind and destroy cancer cells.

The open-access journal Nature Communications recently published a research study focusing on the effectiveness of engineered cytotoxic T cells in cancer treatment. The study assessed the T cells’ ability to successfully overcome physical barriers that they meet while infiltrating a tumor.

Dr. Paolo Provenzano is the study’s senior author. He currently works at the University of Minnesota College of Science and Engineering as an associate professor of biomedical engineering. Along with his research team, Dr. Provenzano created engineering design criteria with the goal of enhancing T cells so that they can reach cancer cells in solid tumors such as pancreatic cancer. T cells struggle to infiltrate solid tumors, which contain tough fibrotic architecture that significantly slows them down.

The researchers implemented genome editing technologies to manipulate the DNA content inside the T cells. By editing T cell genes, the researchers engineered the cells’ microtubule system to improve its effectiveness in overcoming physical barriers in tumors.

Research findings demonstrated that the engineered T cells moved more quickly than natural T cells. Their speed doubled, and they succeeded in infiltrating tumor cells regardless of barriers. Although the study focused on pancreatic cancer in rodents, future clinical trials in human populations diagnosed with other types of cancer can be a promising path in immunotherapy.